Cholinergic anti-inflammatory pathway mediates diesel exhaust PM2.5-induced pulmonary and systemic inflammation

Abstract

Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of research has demonstrated that PM2.5 exposure may induce various negative health effects via pulmonary and systemic inflammations. To study the potential role of the CAP in mediating PM2.5-induced effects, mice were treated with vagus nerve electrical stimulation (VNS) to activate the CAP before diesel exhaust PM2.5 (DEP) instillation. Analysis of pulmonary and systemic inflammations in mice demonstrated that VNS significantly reduced the inflammatory responses triggered by DEP. Meanwhile, inhibition of the CAP by vagotomy aggravated DEP-induced pulmonary inflammation. The flow cytometry results showed that DEP influenced the CAP by altering the Th cell balance and macrophage polarization in spleen, and in vitro cell co-culture experiments indicated that this DEP-induced change on macrophage polarization may act via the splenic CD4+ T cells. To further confirm the effect of alpha7 nicotinic acetylcholine receptor (α7nAChR) in this pathway, mice were then treated with α7nAChR inhibitor (α-BGT) or agonist (PNU282987). Our results demonstrated that specific activation of α7nAChR with PNU282987 effectively alleviated DEP-induced pulmonary inflammation, while specific inhibition of α7nAChR with α-BGT exacerbated the inflammatory markers. The present study suggests that PM2.5 have an impact on the CAP, and CAP may play a critical function in mediating PM2.5 exposure-induced inflammatory response. Availability of data and materialsThe datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.